'Meriwether Lewis’s death has been a source of speculation for many years, often with the mistaken notion that “great men” do not take their own lives, and that suicide blights the memory of a great life. However, those closest to Lewis, Thomas Jefferson and William Clark, fully accepted the reports of suicide. Jefferson reported that Lewis’s family had a history of what is believed to be manic-depression (bipolar disorder), and that he had been subject to bouts of deep depression since his youth.

“Governor Lewis had from early life been subject to hypocondriac [sic] affections. It was a constitutional disposition in all the nearer branches of the family of his name, it was more immediately inherited by him from his father...While he lived with me in Washington, I observed at times sensible depressions of mind, but knowing their constitutional source, I estimated their course by what I had seen in the family.”

Clark likewise reported that Lewis had bouts with euphoria and depression prior to his death, had become deeply in debt, drank heavily and possibly used opium–all symptoms of bipolar disorder. When Lewis’s integrity was questioned over billing as a result of his time as Governor of Louisiana, he left St. Louis deeply troubled and attempted suicide on the boat ride south. A few days later, October 9, 1809, at a small inn on the Natchez Trace southwest of Nashville, Lewis apparently shot himself in despair.

It should be noted, however, that there is the possibility that Lewis suffered from malaria, a disease that is known, in its later stages, to cause forms of dementia and erratic behavior. Whether from depression or malaria, Lewis’s death at so young an age was a tragedy of the first order. It also caused him to be relatively forgotten by the public at large until the end of the 19th century, when historians and the public again looked at the remarkable achievements of the Corps of Discovery, its Captains, and especially Meriwether Lewis himself.'